EULAR recommendations for the management of large-vessel vasculitis.

Objectives: To develop European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis. Methods: An expert group (10 rheumatologists, 3 nephrologists, 2 immunolgists, 2 internists representing 8 European countries and the USA, a clinical epidemiologist and a representative from a drug regulatory agency) identified 10 topics for a systematic literature search through a modified Delphi technique. In accordance with standardised EULAR operating procedures, recommendations were derived for the management of large vessel vasculitis. In the absence of evidence, recommendations were formulated on the basis of a consensus opinion. Results: Seven recommendations were made relating to the assessment, investigation and treatment of patients with large vessel vasculitis. The strength of recommendations was restricted by the low level of evidence and EULAR standardised operating procedures. Conclusions: On the basis of evidence and expert consensus, management recommendations for large vessel vasculitis have been formulated and are commended for use in everyday clinical practice.

Outcomes from studies of Antineutrophil Cytoplasm Antibody Associated Vasculitis: a systematic review by the European League Against Rheumatism systemic vasculitis task force.

Objectives: We undertook a systematic literature review as a background to the European League Against Rheumatism (EULAR) recommendations for conducting clinical trials in anti-neutrophil cytoplasm antibody associated vasculitis (AAV), and to assess the quality of evidence for outcome measures in AAV. Methods: Using a systematic Medline search, we categorised the identified studies according to diagnoses. Factors affecting remission, relapse, renal function and overall survival were identified. Results: A total of 44 papers were reviewed from 502 identified by our search criteria. There was considerable inconsistency in definitions of end points. Remission rates varied from 30% to 93% in Wegener granulomatosis (WG), 75% to 89% in microscopic polyangiitis (MPA) and 81% to 91% in Churg¿Strauss syndrome (CSS). The 5-year survival for WG, MPA and CSS was 74¿91%, 45¿76% and 60¿97%. Relapse (variably defined) was common in the first 2 years but the frequency varied: 18% to 60% in WG, 8% in MPA, and 35% in CSS. The rate of renal survival in WG varied from 23% at 15 months to 23% at 120 months. Methods used to assess morbidity varied between studies. Ignoring the variations in definitions of the stage of disease, factors influencing remission, relapse, renal and overall survival included immunosuppressive therapy used, type of organ involvement, presence of ANCA, older age and male ender. Conclusions: Factors influencing remission, relapse, renal and overall survival include the type of immunosuppressive therapy used, pattern of organ involvement, presence of ANCA, older age and male gender. Methodological variations between studies highlight the need for a consensus on terminology and definitions for future conduct of clinical studies in AAV.

EULAR recommendations for the management of primary small and medium vessel vasculitis.

Objectives: To develop European League Against Rheumatism (EULAR) recommendations for the management of small and medium vessel vasculitis. Methods: An expert group (consisting of 10 rheumatologists, 3 nephrologists, 2 immunologists, 2 internists representing 8 European countries and the USA, a clinical epidemiologist and a representative from a drug regulatory agency) identified 10 topics for a systematic literature search using a modified Delphi technique. In accordance with standardised EULAR operating procedures, recommendations were derived for the management of small and medium vessel vasculitis. In the absence of evidence, recommendations were formulated on the basis of a consensus opinion. Results: In all, 15 recommendations were made for the management of small and medium vessel vasculitis. The strength of recommendations was restricted by low quality of evidence and by EULAR standardised operating procedures. Conclusions: On the basis of evidence and expert consensus, recommendations have been made for the evaluation, investigation, treatment and monitoring of patients with small and medium vessel vasculitis for use in everyday clinical practice.

Identification of haptoglobin as an angiogenic factor in sera from patients with systemic vasculitis.

Angiogenesis is an important process in chronic inflammatory diseases. We observed that sera from patients with systemic vasculitis stimulated angiogenesis in an in vitro model using human umbilical vein endothelial cells cultured on a basement membrane (Matrigel) substrate. After 40% ammonium sulfate precipitation, angiogenic activity remained in the low molecular weight fraction and could be inactivated by heat. SDS-page of serum FPLC fractions exhibiting maximal angiogenic activity demonstrated two prominent species of 45 and 16-20 kD in patients' sera. These bands were much less apparent in sera obtained from control subjects. Amino-terminal sequencing of the 45-kD protein demonstrated that it was haptoglobin. Purified haptoglobin stimulated angiogenesis in a dose-dependent manner. The angiogenic activity of vasculitis patients' sera was partially inhibited by an antihaptoglobin antibody. Furthermore, serum haptoglobin levels in vasculitis patients correlated both with disease and angiogenic activity. Haptoglobin angiogenic activity was confirmed in two in vivo models using an implanted disc and a subcutaneous injection of basement membrane. Stimulation of angiogenesis is a newly recognized biological function of haptoglobin. The increased levels of haptoglobin found in chronic inflammatory conditions may play an important role in tissue repair. In systemic vasculitis, haptoglobin might also compensate for ischemia by promoting development of collateral vessels.

Estudio de la patogenia de clostridium perfringens tipo b y d en pequeños rumiantes

Proyecto de investigación realizado a partir de una estancia en la University of California, Davis, Estados Unidos, entre octubre y desembre del 2007. Clostridium perfringens (C. perfringens) tipo C causa enteritis necrotizante en humanos y enterotoxemias en animales domésticos. Esta bacteria produce beta toxina (CPB), alfa toxina (CPA) y perfringolisina (PFO) durante la fase logarítimca de crecimiento. En nuestro estudio se evaluó la relación entre CPB y la virulencia del aislamiento CN3685 de Cl. perfringens tipo C en un modelo caprino con inoculación intraduodenal. De manera similar a la infección natural por C. perfringens tipo C, el cultivo vegetativo del tipo salvaje de CN3685 provocó dolor abdominal, diarrea hemorrágica, enteritis necrotizante, colitis, edema pulmonar, hidropericardio y muerte en 2 cabritos, a las 24 horas postinoculación. Por otro lado, mediante tecnología Targe Tron® se prepararon mutantes isogénicos carentes de toxina CPB, los cuales fueron inoculados siguiendo el modelo anteriormente descrito. Los resultados mostraron que estos mutantes carecían de todo tipo de virulencia, ya que no se observaron signos clínicos durante las primeras 24 h postinoculación ni tampoco lesiones macroscópicas ni histopatológicas. Posteriormente se desarrolló un modelo experimental similar a los anteriores, en los que se había repuesto la capacidad de producción de CPB en los mutantes. Los dos animales inoculados con estos mutantes complementarios presentaron signos clínicos y lesiones similares a las observadas en el caso del tipo salvaje. Estos resultados muestran que la toxina CPB es necesaria y suficiente para inducir la enfermedad causada por CN3685. Esto a su vez, demuestra la importancia de este tipo de toxina en la patogénesis de C. perfringems tìpo C.

Asociación del anticuerpo anti-C1q con las manifestaciones clínicas, hematológicas e inmunológicas en el Lupus Eritematoso Sistémico: Estudio observacional retrospectivo de 135 casos.

: Las concentraciones de anticuerpo anti-C1q están elevadas en los pacientes afectados de LES. Según algunos estudios la presencia de este anticuerpo está asociada a la nefropatía lúpica, sin embargo en otros estudios esta relación no se comprobó. En nuestro trabajo relacionamos la positividad del anticuerpo anti-C1q con las manifestaciones clínicas, hematológicas e inmunológicas de la enfermedad. A diferencia de estudios previos sólo pudimos establecer una relación estadísticamente significativa con la vasculitis (p&0.001), la presencia de anti-DNAds (p 0.034), de anti-Sm (p 0.045) y el consumo de C3 (p 0.006). Se observó que los pacientes anti-C1q positivos desarrollan la enfermedad a edades más tempranas que los pacientes anti-C1q negativos. (p &0.005).

Granulomatosis de Wegener: estudio de 15 casos, supervivencia y daño crónico

La granulomatosi de Wegener i la síndrome de Churg-Strauss són vasculitis granulomatoses de petit i mitjà vas. Es diagnostiquen mitjançant clínica i biòpsia compatible, i s'associen amb anticossos anticitoplasma de neutròfils. S'ha realitzat un estudi retrospectiu (1984 - 2010) a l'Hospital Universitari Germans Trias i Pujol. Es presenten 15 pacients amb granulomatosi de Wegener. Les característiques clíniques de la present sèrie no difereixen de les descrites prèviament. Es va comparar la supervivència i el dany crònic acumulat en els pacients amb aquestes dues vasculitis. Tant la mortalitat com el dany crònic acumulat resultà superior en el grup de malalts amb granulomatosi de Wegener.

Poliangeitis amb Granulomatosis eosinofílica i asma al•lèrgica; dues monedes amb una mateixa cara?

La síndrome de Churg-Strauss o Poliangeitis amb Granulomatosis eosinofílica (EGPA), clàssicament s’ha vinculat a un substrat asmàtic d’origen al•lèrgic. No obstant, l’evidència en aquest sentit és equívoca. L’objectiu d’aquest treball és identificar diferències clíniques i serològiques entre pacients amb EGPA i pacients asmàtics al•lèrgics, i determinar el perfil al•lèrgic d’un grup de pacients diagnosticats d’EGPA. Es comparen dos grups de pacients: un grup de diagnosticats d’EGPA, i un altre amb asma al•lèrgic. Malgrat les similituds clíniques entre els dos grups, les reaccions immunoal•lèrgiques no semblen intervenir en la fisiopatologia de la majoria dels casos d’EGPA.

Pure sensory neuropathy in patients with primary Sjogren's syndrome: clinical, immunological and electromyographic findings

A pure sensory neuropathy caused by lymphocytic infiltration of the dorsal root ganglia has been reported in a few patients with Sjögren's syndrome. The clinical, immunological, and electromyographic findings of five patients with this type of neuropathy and primary Sjögren's syndrome were reviewed. Typical clinical indications were the presence of a chronic asymmetrical sensory deficit, initial disease in the hands with a predominant loss of the vibratory and joint position senses, and an association with Adie's pupil syndrome or trigeminal sensory neuropathy. The simultaneous impairment of the central and peripheral evoked cortical potentials suggested that there was a lesion of the neuronal cell body. The neuropathy preceded the diagnosis of Sjögren's syndrome in four patients. Four patients were positive for Ro antibodies, but systemic vasculitis or malignancy was not found after a mean follow up of six years. These findings indicate that in patients with a sensory neuropathy the diagnosis of Sjögren's syndrome has to be considered, even if the patient denies the presence of sicca symptoms, and that appropriate tests must be carried out.

Systemic lupus erythematosus in men: clinical and immunological characteristics.

Although systemic lupus erythematosus (SLE) has traditionally been considered a disease of women, men may also be affected. Thirty of 261 patients (12%) with SLE seen in this hospital were men. Arthritis was less common as a first symptom in the men, although this group of patients had discoid lesions and serositis more often than the women. During the follow up a lower incidence of arthritis and malar rash and a higher incidence of other skin complications including discoid lesions and subcutaneous lupus erythematosus was found in the men. The incidence of nephropathy, neurological disease, thrombocytopenia, vasculitis, and serositis, was similar in the two groups. No significant immunological differences were found between men and women. These features indicate that several gender associated clinical differences may be present in patients with SLE.